Direct excitation of spinal GABAergic interneurons by noradrenaline

Matthias Gassner, Ruth Ruscheweyh, Jürgen Sandkühler
2009 Pain  
Endogenous pain control is, in part, mediated by descending inhibition of spinal nociception via spinal release of noradrenaline. Antinociception by activation of descending noradrenergic fibres has partially been attributed to the direct inhibition of nociceptive spinal neurons. Here, we tested the alternative hypothesis: the direct excitation of inhibitory spinal interneurons by noradrenaline. Transverse lumbar spinal cord slices were obtained from adult mice expressing enhanced green
more » ... anced green fluorescent protein (EGFP) in GABAergic neurons under control of the GAD67 promoter. Recordings were made from a total of 113 EGFP-expressing neurons and non-EGFP-expressing neurons in spinal laminae II and III with the perforated patch-clamp technique. In lamina II, where mainly nociceptive afferents terminate, noradrenaline (20 lM) depolarised significantly more EGFP-labelled (41%) than non-EGFP-labelled GABAergic neurons (4%). In contrast, noradrenaline hyperpolarised significantly more non-EGFP-labelled (46%) than EGFPlabelled GABAergic neurons (20%). In lamina III, where low threshold afferents terminate, EGFP-labelled neurons were never depolarised but either hyperpolarised (25%) or not affected (75%) by noradrenaline. Depolarisations of EGFP-labelled lamina II neurons were mimicked by the a 1 -adrenoceptor agonist phenylephrine (10-20 lM) and abolished by the a 1 -adrenoceptor antagonist prazosin (2 lM). Hyperpolarisations of EGFP-and non-EGFP-labelled neurons were abolished by the a 2 -adrenoceptor antagonist yohimbine (2 lM). These results show that noradrenaline directly excites inhibitory (GABAergic) lamina II interneurons in addition to its inhibitory effect on (putatively excitatory) interneurons in superficial spinal dorsal horn. Both effects of noradrenaline constitute a synergism in descending inhibition of nociceptive information in the spinal dorsal horn. Ó
doi:10.1016/j.pain.2009.06.021 pmid:19608344 fatcat:wigynkhe3fcyzjn77fxmctmnqq